This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We compared the in vivo infectivity and pathogenicity of a CCR5-tropic SHIV-SF162 P4 in rhesus and pig-tailed macaques. Twelve pig-tailed macaques were inoculated intrarectally with SHIVSF162 P4 at 1,800 or 360 TCID50 (6 animals/dose). A parallel study with rhesus inoculated with an identical stock of virus was done at the CaNPRC. Plasma viremia was measured by real time RNA PCR and peripheral blood CD4 T cell count determined by immunophenotyping. SHIVSF162 P4 showed identical infectivity by the intrarectal route in rhesus and pigtailed macaques, since all six animals inoculated with the high dose and 5/6 animals with the low dose were infected, regardless of species tested. The mean peak viral load was also similar between the two species (1. 7 x 107 copies/ml of plasma in rhesus vs. 2.1 x 107 in pigtails). However, 4/11 of the infected pigtails had persistent plasma viral load GT 104 copies/ml. This was in contrast to infected rhesus, where none of the animals showed detectable plasma viremia beyond wk 8. Two of the 4 pigtails that had persistent viral load showed progressive peripheral blood CD4 T cell decline, with one developing AIDS-like diseases within 15 months after infection. On the other hand, none of the infected rhesus showed any change in CD4 T cell count from pre-inoculation levels. Together, these results indicate that both rhesus and pig-tailed macaques are similarly susceptible to SHIV-SF162 P4 infection by mucosal routes. However, SHIV replication was significantly more robust in pig-tailed macaques than in rhesus. These findings underscore the value and the importance of diversity different hosts when comparing vaccine efficacy and studying pathogenesis in macaque species.